The clinical fields of orthopedics and traumatology deal with the reconstruction and preservation of the injured musculoskeletal system and associated organs. Implant loosening, migration, cut-out, as well as, infection control play a major role in complications that may occur post-surgery. In general, hydroxyapatite (HA) is a common material used for biomedical applications. HA coatings are known to be biocompatible, osteoconductive and typically enhance osseointegration of implants and therefore contribute towards more rapid and enhanced fixation. See Allegrini S et al., “Hydroxyapatite Grafting Promotes New Bone Formation and Osseointegration of Smooth Titanium Implants” Ann Anat 188 143-51 (2006) and Baker K. et al., “Growth, Characterization and Biocompatibility of Bone-like Calcium Phosphate Layers Biomimetically Deposited on Metallic Substrata” Mater Sci Eng 26 1351-60 (2006).
Hydroxyapatite can be deposited onto surgical implants by different processes, such as, biomimetic deposition from aqueous solution, plasma-spraying, electrophoretic deposition, sol-gel processes or dip-coatings temperature, each resulting in process dependent coating characteristics. See Forsgren J. et al, Acta Biomater; Wang M. J. et al., “Electrophoretic Deposition of Porous Hydroxyapatite Scaffold” Biomaterials 24 3505-10 (2003) and Dean-Mo L. et al. “Water-based Sol-Gel Synthesis of Hydroxyapatite: Process Development” Biomaterials” 22 1721-30 (2001).
The nanoporous structure of biomimetic HA coatings have shown promising properties for drug incorporation and with respect to local drug delivery. See U.S. Provisional Patent Application No. 61/814,538. HA coatings can provide an excellent carrier for various water soluble drugs. See Forsgren J. et al., “Co-loading of Bisphosphonates and Antibiotics to a Biomimetic Hydroxyapatite Coating” Biotechnol Lett 33 1265-68 (2011).
The local release of drugs from calcium phosphate based materials and functional HA implants coatings enable favorable enhancement of local bone tissue regeneration in-vivo See Abtahi J. et al., “A Bisphosphonate-Coating Improves the Fixation of Metal Implants in Human Bone—A Randomized Trial of Dental Implants” Bone 50 1148-51 (2012) and Tengwall P. et al., “Surface Immobilized Bisphosphonate Improves Stainless-steel Screw Fixation in Rats” Biomaterials 25 2133-8 (2004), as well as to prevent early bacterial colonization and biofilm formation, see Ginebra M. et al., “Calcium Phosphate Cements as Bone Drug Delivery Systems: A Review” J Control Release 113 102-10 (2006).
Most approaches for incorporating drugs into porous calcium phosphates or HA coatings focus on adsorptive loading techniques from drug containing aqueous solutions. Incorporation of drugs into the porous HA coating structure can be done by soaking of the HA coated implant in the drug containing solution. See Brohede U. et al., “Multifunctional Implant Coatings Providing Possibilities For Fast Antibiotics Loading with Subsequent Slow Release” J Mater Sci-Mater Med 20 1859-67 (2009). To date an antibiotic release over a period of 8 days has been demonstrated from adsorption-loaded HA coatings deposited on fixation pins, while the longest antibiotic effect demonstrated so far does not exceed 3 days. See Lilja, M. et al., “Photocatalytic and Antimicrobial Properties of Surgical Implant Coatings of Titanium Dioxide Deposited Through Cathodic Arc Evaporation” Biotechno Lett 12 2299-305.2 (2012).
Co-precipitation, incorporating drugs simultaneously during biomimetic growth of the coating, in contrast, offers the possibility to incorporate drugs during coating growth and, hence, constitutes a promising method for producing functional drug containing coatings in a single step process. The drug concentration in the buffer solution, as well as, the chemical and molecular structure of the drug has been shown to be critical parameters impacting the coating growth and the drug content of such coatings. See Åberg J. et al., “Bisphosphonate Incorporation in Surgical Implant Coatings by Fast Loading and Co-precipitation at Low Drug Concentrations” J Mater Sci-Mater 20 2053-61 (2009) . Thus, the initial nucleation and growth of drug-containing HA remains a challenging and not fully understood process step.